ADC Therapeutics Announces FDA Approval of ZYNLONTA™ (loncastuximab tesirine-lpyl) in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Rhea-AI Summary

ADC Therapeutics SA (NYSE: ADCT) announced FDA approval for ZYNLONTA™ (loncastuximab tesirine-lpyl) to treat adult patients with relapsed or refractory large B-cell lymphoma after multiple therapies. This accelerated approval is based on a 48.3% overall response rate from the pivotal LOTIS-2 trial. The trial included 145 patients, revealing a complete response rate of 24.1%. ZYNLONTA's commercial launch in the U.S. is imminent, alongside an Advancing Patient Support Program for eligible patients. However, continued approval is dependent on further clinical benefit verification.

Positive

• FDA approval for ZYNLONTA provides a new treatment option for r/r DLBCL patients.
• Overall response rate of 48.3% in pivotal LOTIS-2 study indicates strong efficacy.
• Commercial availability in the U.S. will enhance market presence and revenue potential.

Negative

• Continued approval of ZYNLONTA is contingent on further clinical trials to verify clinical benefits.

ADC Therapeutics SA (NYSE: ADCT) today announced that the U.S. Food and Drug Administration (FDA) has approved ZYNLONTA™ (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low grade lymphoma and high-grade B-cell lymphoma.¹ ZYNLONTA, a CD19-targeted antibody drug conjugate (ADC), has been granted accelerated approval by the FDA based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

“There is a significant unmet need for treatment options for patients with r/r DLBCL, including those who have been heavily pretreated and have difficult-to-treat disease,” said Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University. “Single-agent ZYNLONTA demonstrated clinically important outcomes in the pivotal LOTIS-2 study across several disease subtypes. Notably, this included transplant eligible and ineligible patients and patients who previously received stem cell transplant or CAR-T cell therapy.”

The FDA approval was based on data from LOTIS-2, a large (n=145) Phase 2 multinational, single-arm clinical trial of ZYNLONTA for the treatment of adult patients with r/r DLBCL following two or more prior lines of systemic therapy. Results from the trial demonstrated an overall response rate (ORR) of 48.3% (70/145 patients), which included a complete response (CR) rate of 24.1% (35/145 patients) and a partial response (PR) rate of 24.1% (35/145 patients). Patients had a median time to response of 1.3 months and the median duration of response (mDoR) for the 70 responders was 10.3 months (inclusive of patients who were censored). In a pooled safety population the most common adverse reactions (≥20%) were thrombocytopenia, gamma-glutamyltransferase increased, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea and musculoskeletal pain. In LOTIS-2, the most common (≥10%) grade ≥3 treatment-emergent adverse events were neutropenia (26.2%), thrombocytopenia (17.9%), gamma-glutamyltransferase increased (17.2%) and anemia (10.3%).

“The FDA approval of ZYNLONTA is an exciting advancement for patients with r/r DLBCL and a transformational event for ADC Therapeutics,” said Chris Martin, Chief Executive Officer of ADC Therapeutics. “We extend our deepest gratitude to the patients who participated in our LOTIS-1 and LOTIS-2 clinical trials, their families, the study investigators and our employees, as their commitment made this important milestone possible.”

DLBCL, the most common type of non-Hodgkin lymphoma in the United States, is a rapidly progressing, aggressive disease that is heterogeneous with multiple subtypes.² More than 40% of first-line DLBCL treatments fail.³ For patients who fail first-line therapy, prognoses are poor, worsening with each line of therapy as the chance for cure or long-term disease-free survival diminishes.^4,5

ZYNLONTA will be commercially available in the United States shortly. ADC Therapeutics has launched the Advancing Patient Support Program, a comprehensive patient support program offering financial assistance, ongoing education and other resources to eligible patients who are prescribed ZYNLONTA.

Please see full Prescribing Information at www.adctherapeutics.com for ZYNLONTA.

Conference Call Details

ADC Therapeutics management will host a conference call and live audio webcast on Friday, April 23, 2021 at 4 p.m. ET. To access the live call, please dial (833) 303-1198 (domestic) or +1 914 987 7415 (international) and provide conference ID 6867157. The live webcast will be available under “Events & Presentations” in the Investors section of the ADC Therapeutics website at ir.adctherapeutics.com. The archived webcast will be available for 30 days following the call.

Important Safety Information

WARNINGS AND PRECAUTIONS

Effusion and Edema
Serious effusion and edema occurred in patients treated with ZYNLONTA. Grade 3 edema occurred in 3% (primarily peripheral edema or ascites) and Grade 3 pleural effusion occurred in 3% and Grade 3 or 4 pericardial effusion occurred in 1%.

Monitor patients for new or worsening edema or effusions. Withhold ZYNLONTA for Grade 2 or greater edema or effusion until the toxicity resolves. Consider diagnostic imaging in patients who de

FAQ

What is ZYNLONTA approved for?

ZYNLONTA is approved for treating adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy.

What were the results of the LOTIS-2 trial for ZYNLONTA?

The LOTIS-2 trial showed an overall response rate of 48.3%, with a complete response rate of 24.1%.

When will ZYNLONTA be available commercially?

ZYNLONTA will be commercially available in the United States shortly after FDA approval.

What are the common side effects of ZYNLONTA?

Common side effects include thrombocytopenia, neutropenia, anemia, and increased gamma-glutamyltransferase.

How does ZYNLONTA benefit patients with DLBCL?

ZYNLONTA offers a new treatment avenue for patients with limited options following multiple lines of therapy.